Furthermore, we show that growth factor-initiated phosphatidyl-3-kinase (PI3K), protein kinase B (PKB)/Akt, and mammalian target of rapamycin (mTOR) cell signaling pathways, along with oncogenes and transcription factors such as KRAS, c-Myc, and p53 interplay with HIF-1 and AMPK, as well as ROS generation, to enable cancer cell metabolic plasticity. This evidence concerns the gene HIF1A and cancer.